DESCRIPTION (adapted from the application) Candidate: Dr. Kevin Olbrich has a background in Biomedical Engineering and Materials Science. He has recently been appointed to the position of Assistant Research Professor of Surgery and Duke University Medical Center. Mentors: Dr. Bruce Klitzman, an expert in microvascular physiology and Dr. Doris Taylor, an expert in molecular biology techniques, will serve as mentors on this project. Career Development Goals: My immediate goal is to develop a strong research program in tissue engineering with an emphasis on transport cells in diffusion chambers. My long-term goal is to develop an integrated program in bioartificial organ development. My career development plans include in-depth training in molecular biology techniques and microvascular physiology. Environment: I am fortunate to be affiliated with the Center for Cellular and Biosurface Engineering at Duke University as well as the Dept. of Surgery at the Duke University Medical Center. There are numerous opportunities for collaboration with faculty from all parts of the university and medical center. Some collaboration will assist in the completion of the aims of this research project. Research: Due to the extreme shortage of organ donors, the development of a bioartificial pancreas has been aggressively sought. These devices encapsulate porcine islet tissue within an immunoisolation membrane, which protects them from the immune system of the implant recipient. Unfortunately, the survival of islet tissue within such devices is poor. Immediately after transplantation, the encapsulated tissue suffers from post-transplantation ischemia due to the lack of blood supply to the implanted device. This condition will persist for 4-10 days, during which time much of the encapsulated tissue will die. The first aim of this proposal is to investigate the role of hypoxia-induced apoptosis and stress protein production in implantable diffusion chambers and to develop interventions that will protect the encapsulated tissue during the post-transplantation ischemia. Once tissue has survived the initial implantation, it must contend with long-term transport insufficiency due to the formation of an avascular fibrous capsule around the diffusion chamber. The second aim of this project is to inhibit fibrous capsule formation by administration of collagen synthesis inhibitors, and to improve local vascular density by 1) infecting the tissue surrounding the implant with an adenoviral vector for vascular endothelial growth factor (VEGF), 2) encapsulating cells genetically modified to produce VEGF, 3) implanting syngeneic cells modified to produce VEGF around the implanted device. The results of this project will provide valuable information for improving the bioartificial pancreas. This award will permit me to achieve my immediate goal of establishing a strong research program in tissue engineering.